Thread by @PeacockFlu

As its been getting increasing attention recently, I'm going to write a short thread on what we currently know about BA.2.
-what is BA.2?
-what is BA.2 doing currently?
-Should we be concerned about it?

First off - what is BA.2?

BA.2 is a sister lineage to BA.1. Currently both lineages are defined as the Omicron variant.

As @shay_fleishon shows - BA.2 shares a lot of mutations with BA.1, but it also has many differences

https://twitter.com/shay_fleishon/status/1480934070012059649

BA.2 also lacks the Spike Δ69-70 mutations that means it does not cause S gene target failure in the taqman qPCR assay. This assay was used early on in the Omicron wave to estimate how rapidly BA.1 spread. This is why BA.2 was misdescribed as a 'stealth variant' early on.

Next what is BA.2 currently doing?

BA.2 appears to be the major Omicron lineage in (part of) India and the Philippines and there is evidence it is growing compared to BA.1 in Denmark, the UK and Germany as shown nicely by @CorneliusRoemer below

https://twitter.com/CorneliusRoemer/status/1482833651276697612

Consistant growth across multiple countries is evidence BA.2 may be some degree more transmissible than BA.1. This is the main reason BA.2 is currently in the news.

Unfortunatley this is really where the evidence mostly ends - we do not currently have a strong handle on antigenicity, severity or a much evidence for how much more transmissibility BA.2 might have over BA.1 - however we can make some guesses/early observations

*Very* early observations from India and Denmark suggest there is no dramatic difference in severity compared to BA.1. This data should become more solid (one way or another) in the coming weeks.

Some predictions by @jbloom_lab suggest the Spike RBD mutations are likely to have a fairly minimal impact on antigenicity compared to BA.1.

https://twitter.com/jbloom_lab/status/1470442877494824961

I would also agree with this that there is likely to be minimal differences in vaccine effectiveness against BA.1 and BA.2 and, its also highly likely BA.1 infection will give decent cross-reactivity against BA.2 infection.

So how worried should we be? Those working in sequencing/surveillence should definitley be keeping a close eye on BA.2 (and very likely already are!). Personally, I'm not sure BA.2 is going to have a substancial impact on the current Omicron wave of the pandemic...

Several countries are near, or even past the peak of BA.1 waves. I would be very surprised if BA.2 caused a second wave at this point. Even with slightly higher transmissibility this absolutely is not a Delta -> Omicron change and instead is likely to be slower and more subtle.

That said I wouldnt be that surprised if BA.2 slowly replaces BA.1 over the coming months with a slightly 'optimised' mutational profile (think a more extreme version of AY.4.2 vs Delta in the UK). That said this is just a prediction and could be quite wrong...

Several folks are closely monitoring the BA.2 situation - for more updates/info, and a range of opinions would recommend following @JosetteSchoenma @shay_fleishon and @CorneliusRoemer who are putting in great work monitoring this variant.

One final post I forgot to add - nearly all literature on Omicron is done using BA.1. Virology labs worldwide are currently scrambling to assess BA.2 (and see if it does the same as BA.1) - I suspect lab data will start appearing in next couple of weeks.

Update 1: @UKHSA has designated BA.2 a VUI (similar to WHO catagory VOI), separate from BA.1 due to the continuing growth in the UK.

https://twitter.com/UKHSA/status/1484494667551059975

Update 2: Preliminary VE from UKHSA - suggests minimal differences in VE between Omicron variants (actually trending slightly towards greater VE against BA.2 than BA.1).

https://twitter.com/PaulMainwood/status/1486712480982130696

BA.2 update 3:
- Solid evidence for BA.2 being more transmissible than BA.1(.1)
- Similar vax effectiveness for BA.2 and BA.1
- BA.1 gives good, but not perfect protection from BA.2 re-infection
- BA.2 does *not* appear to be more severe than BA.1 in real world cohorts.

regarding animal models - a study is out today showing no difference in BA.1 and BA.2 pathogenicity in mice and hamsters using live virus isolates - this is different from what was found in hamsters infected with spike-only chimeric viruses last week. researchsquare.com/article/rs-137…

This difference is really interesting and implies BA.2 (and maybe BA.1) might have some mutations outside of spike that lead to its lower severity (in animal models at least). This has sort of been implied by a few studies looking at Omicron mutations in other genes (E and M)

The real world severity data (showing little difference in severity) is from South Africa and the UK, with further data described in the latest WHO press report as from Denmark. who.int/news/item/22-0…

Overall its worth reiterating:
Enhanced transmissibility alone *will* cause some issues - potentially causing prolonged peaks (maybe what is being seen in Denmark?) or slowing down/transiently reversing of declines (worth watching the UK data closely in the next few weeks...)

However, most of the evidence so far is pointing towards BA.2 acting fairly consistantly with BA.1 - Personally I think there continues to be a fairly good arguement for these both to remain as two halves of Omicron (though I can understand arguments against this as well).